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Published at www.nejm.org February 6, 2008 (10.1056/NEJMoa073785)

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ABSTRACT

Background Three patients who received visceral-organ transplants from a single donor on the same day died of a febrile illness 4 to 6 weeks after transplantation. Culture, polymerase-chain-reaction (PCR) and serologic assays, and oligonucleotide microarray analysis for a wide range of infectious agents were not informative.

Methods We evaluated RNA obtained from the liver and kidney transplant recipients. Unbiased high-throughput sequencing was used to identify microbial sequences not found by means of other methods. The specificity of sequences for a new candidate pathogen was confirmed by means of culture and by means of PCR, immunohistochemical, and serologic analyses.

Results High-throughput sequencing yielded 103,632 sequences, of which 14 represented an Old World arenavirus. Additional sequence analysis showed that this new arenavirus was related to lymphocytic choriomeningitis viruses. Specific PCR assays based on a unique sequence confirmed the presence of the virus in the kidneys, liver, blood, and cerebrospinal fluid of the recipients. Immunohistochemical analysis revealed arenavirus antigen in the liver and kidney transplants in the recipients. IgM and IgG antiviral antibodies were detected in the serum of the donor. Seroconversion was evident in serum specimens obtained from one recipient at two time points.

Conclusions Unbiased high-throughput sequencing is a powerful tool for the discovery of pathogens. The use of this method during an outbreak of disease facilitated the identification of a new arenavirus transmitted through solid-organ transplantation.

Source Information

From the Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York (G.P., T.B., S.C., P.-L.Q., J.H., W.I.L.); Victorian Infectious Diseases Reference Laboratory, Victoria, Australia (J.D., T.T., C.B., J.M., M.C.); 454 Life Sciences, Branford, CT (L.D., J.F.S., M.E.); and the Centers for Disease Control and Prevention, Atlanta (C.D.P., W.-J.S., C.S.G., S.R.Z.).

Drs. Palacios and Druce contributed equally to this article.

This article (10.1056/NEJMoa073785) was published at www.nejm.org on February 6, 2008. It will appear in the March 6 issue of the Journal.

Address reprint requests to Dr. Lipkin at the Center for Infection and Immunity, Mailman School of Public Health, Columbia University, 722 W. 168th St., New York, NY 10032, or at wil2001{at}columbia.edu, or to Dr. Catton at the Victorian Infectious Diseases Reference Laboratory, Locked Bag 815, Carlton South, Victoria 3053, Australia, or at mike.catton{at}mh.org.au.

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